Oxides of diazabicyclo-octane



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3,038,903 OXIDES F DIAZAEBICYCLDOCTANE Adalbert Farkas, Media, Pm, and Elbert C. Herrick,

Wilmington, Del., assignors to Air Products and Chem- EXAMPLE II Another batch of product was prepared similarly to that of Example i above using approximately mol for mol quantities of diazabicyclo-octane and hydrogen peroxide sg fig ii g i fi ig ggg g2 ig g si f N 0' 808,576 (with peroxide in slight excess) The diazabicyclo-octane Claims. was used as an aqueous solution of 5 mols/liter and the peroxide was employed as a 30% solution.

The present invention relates to monoand dioxides of QM admixture of the two solutions an exothermic re- 1,4-diazahicyclo-2,2,2-octane as new compositions of matachOn s e dent and the mixture became quite warm. I methods for preparation of the same, About another 1A; volume 0f W316i W38 added and the di- The starting material, 1,4-diazabicyclo-2,2,2-octane, also hltcd mlxhll'e permitted to Sta-11d Overnightknown as triethylene-diamine, is described in the literature. The p u did not crystallize but pp as a More recently it has become available in commercial quan- P clear q Which was further evaporated by heattities, prepared by methods described in U.S. application 15 mg on a steam bath with a jet of air directed at the prod- Serial No. 628,723, filed December 17, 1956, now Patent tc o s n added (p not dissolved) No, 2,931,176, According t an example ther i 1 and the slurry further heated on the steam bath for one scribed, the aforesaid compound is obtained in acceptable 011 00011118, 1116 material d fi d to an acetoneyields by vapor phase cyclization of aliphatic amines, for n uble mass, which 011 y g formed a White y example, diethyl-ene triamine, over acidic silica-alumina oplc powder. catalyst, at a temperature of about 675 F., and separation A P0r 10n Of the product Was further dried under vac- Of the desired reaction product from accompanying piper- 1111111 while being heated n a a r hflth- Samples of the azine compounds formed and from other minor reaction ooled product Were analyzed. lay-products.

The novel compounds of the present invention correspond respectively to the formula:

0 Found Calcu- IL} (avg. anallated for t Ethical HZC/ (IJ $0132 percen Hit; iHi hm g 9.0 9.4 h N" 33:3 2?:3 1 O (by balance) 15. 5 12.5 and 35 100. 0 100. 0

N H:?/(IEE(IJH2 Heo\( 3H i CH: The above analysis gave a slightly high value for oxygen, N indicating that either some water or a small amount of the dioxide compound was probably present in addition to the monoxide.

The monoxide has been prepared in essentially quantita- XAMPLE III tive yields by mild oxidation of diazabicyclo-octane at l room temperature with about an equimolar proportion of To a sohmon of ,dlazablcyclo'octane WW) 111 hydrogen pemxith By employing 2 mols a Slight water (4 mols per lrter) there was added a solut1on of cess above 2 mols of the oxidizing agent per mol of di- 30% hydrogen P an aFwLmt ful'ms'hlng 233 Parts azabicyclo-octane, or by further oxidation of the monby welgh't of the Pemxlde Solutlon excess of molar) oxide, the dioxide is obtained for 224 parts by weight of the diazabicyclo-octane. The

exothermic reaction caused the temperature to rise to 48 EXAMPLE I C. External heat was applied and the temperature To about V2 part by weight of diazabicyclooctane disbrought thereby to which temperature as h solved i 3 parts water th was dd d a substantially for 5 minutes. The water was dis-tilled oflf under vacequal volume of 30% hydrogen peroxide, and the mixture mm in a Still Provided With a y P permitted to stand overnight. The product had crystaland the residue dried under Vacuum g) lized to a whit s lid, .A tt was d to di l with infrared heating. The white residue thus obtained the white solid in benzene on a steam bath which proved was 210 Parts y weight A additional 40 P r s Were unsuccessful. Similarly, the white solid could not be discollected as a Solid on 1116 Walls of the y Ice psolved by heating in acetone to its boiling point. The solid The Pmdllct on "analysis gave the following Values did dissolve readily in water. Analysis showed the solid pared With cal calculations. to conform substantially to the formula weight for the monoxide of diazabicyclo-octane.

C HflNgO Theory Found Calc. for

1935531??? re i ri t b arm a: as Nitr 'en. 21. 9 21. 7 Oxygen 125 g" 56.2 55. 38

3 EXAMPLE IV bubbles of gas were evolved and the temperature of the mixture rose to about 50 C. After all of the peroxide had been added, the mixture was permitted to stand at ambient temperature over the weekend, at which time the 7 hydrogen ion concentration of the solution was tested (with test paper) and found to be about 6 (believed indicative of incomplete oxidation).

Excess hydrogen peroxide was removed by placing platinumalumina catalyst pellets into the solution for a 2- hour period with occasional stirring. About 10 parts by weight of gas were thus evolved. The'solution was again tested for excess of hydrogen peroxide by addition of po tassiurn bichromate (Schumb et al.: Hydrogen Peroxide, Reinhold Publishing Corp, New York, 155, p. 549); no

' excess peroxide was evident.

. The product was dehydrated under vacuum at a temperature of upto 35 C., and the solidsrecovered under nitrogen, weighed. Because the recovered weight indicated the presence of water, the product was again dried under vacuum at temperatures-up to 53 C. The recovered dried product when weighed now approximated theoretical yield for diazabicyclo octane-N,N-dioxide. :The

recovered solid product was soluble in ethanol, but insoluble in ether, benzene and pentane.

Theory, Foimd, CuHflNzOI Percent Percent Diazabicyclo-octane monoxide and dioxide are useful as polymerization inhibitors or stabilizers for unsaturated organic compounds. For example, in stabilizing styrene monomer in storage there may be added 0.01 to 0.1% of the monoor dioxide of diazabicyclo-octane without interfering with most uses to which the styrene is to be put.

The diazabicyclo-octane-N,N-dioxide has been tested (at the US. Air Force Laboratory, Chicago) as a protective agent against radiation injury by Xrays. Administered to experimental mice, it was found to be quite nontoxic, showing no significant lethal efiect in doses of up to 1000 mgm./k-gm. of animal body weight. Very few of the large number of compounds screened for use as protective agents against radiation exposure were of this low toxicity. From data supplied by the U.S.A.F. Laboratory on the N,N-dioxide, a direct comparison with a control shows a definite and valuable improvement in the percentage of survivals among mice shortly after and for an intermediate time after'X-irradiation at a -fatal level (800 r.):

Percentage of Survivals A ftev- X-Irradiation [800 r. whole body irradiation] Days after irradiation Q. 1 l 6 I 8 Percentage survival-d-control 100 60 5O DABCO-N, N-dioxide:

2-500 mgmJkgm. wt 100 90 80 3-l,000 mgm./kgm. Wt 100 100 100 At least two groups of ten mice each were used in each experiment, preselectedfor their healthy condition on the basis of several weeks" observation of weight and other.

characteristics prior to use; The test at the 1000 mgmJ ltgm. dosage showed 100% survival of the injected mice for eight days after exposure as compared to 50% survival of the non-treated controls. The product thus has a demonstrated use in the prevention or postponement of death from severe irradiation. higher dosage levels; These results were deemed of important interest as compared with a large number of compounds also thus tested in the screening experiments in cluding a number of quinone derivatives, nitriles, thio- 'carbamates, etc., many of which were toxic in doses as low as -50 m'gnL/kgm. 1

Obviously many modifications and variations of the 1 present invention as hereinbcfore set forth may be made without departing from the spirit and scope thereof and therefore'only such limitations should be imposed as are indicated in the appended claims.

What is claimed is: I

l. The method of preparing monoand di-N-oxides of diazabieyclo-octane which comprises mildly oxidizing diazabicyclo-octane in aqueous medium with hydrogen peroxide at conditions including a temperature in the range of room temperature to C. and a time period of at least five minutes.

2. The method accordingto claim 1 wherein said hydrogen peroxide is employed in equimolar amount with said diazabicyclo-octane and the product is chiefly the mono-N-oxide'ot diazabicyclo-octane.

3. The method according to claim 1 wherein said hydrogen peroxide is employed in a ratio of at least 2 mols per mol of said diazabicyclo-octane and the product is chiefly the di-N-oxide of diazabicyclo-octane.

4. As a new composition of matter the compound corresponding to the formula:

References Cited in the file of this patent Farkas et al.: Industrial and Engineering Chemistry, vol.

51, pages 1299-1300 (1959).

Enhanced effects are expected at 

5. AS A NEW COMPOSITION OF MATTER THE OXIDATION PRODUCT OF DIAZABICYCLO-OTANE CORRESPONDING TO TH EFORMULA: 